J Thorac Oncol. 2026 Sep 16:104204. doi: 10.1016/j.jtho.2026.104204. Online ahead of print.

ABSTRACT

BACKGROUND: Early-stage EGFR-mutant lung adenocarcinoma (LUAD) demonstrates heterogeneous outcomes after curative surgery, yet adjuvant treatment decisions are guided by pathological stage alone. Following the ADAURA trial, adjuvant osimertinib is the standard of care for resected stage IB-IIIA EGFR-mutant LUAD; however, real-world data demonstrate that up to 40% of patients remain disease-free at five years without adjuvant osimertinib, underscoring the need for improved risk stratification.

PATIENTS AND METHODS: We performed integrated clinical, genomic and transcriptomic profiling of 400 patients with resected stage IA-IIIA EGFR-mutant LUAD. EGFR-mutant recurrence risk models integrating clinical, genomic and transcriptomic data were developed and validated across one internal and three external cohorts.

RESULTS: Genomic instability, including TP53 co-mutations, copy number alterations and APOBEC-associated mutational signatures, increased with pathological stage. RBM10 co-mutations were enriched in tumours with L858R mutations and correlated with upregulation of WNT signalling and epithelial-mesenchymal transition. Transcriptomic features outperformed clinical or genomic variables alone in predicting recurrence risk, and a multi-omic model demonstrated superior and reproducible performance, achieving a median concordance index of 75.4% across four independent validation cohorts. The multi-omic model stratified recurrence risk within individual pathological stages, including stage I disease, and identified patients most likely to benefit from adjuvant EGFR TKI.

CONCLUSIONS: These findings define the molecular heterogeneity of early-stage EGFR-mutant LUAD and support multi-omic risk stratification to inform adjuvant EGFR TKI decisions beyond pathological stage. Prospective validation in larger cohorts will be required to confirm these findings.

PMID:42749051 | DOI:10.1016/j.jtho.2026.104204

J Thorac Oncol. 2026 Mar 26:103696. doi: 10.1016/j.jtho.2026.103696. Online ahead of print.

ABSTRACT

INTRODUCTION: Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early-stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation.

METHODS: The Asian Thoracic Oncology Research Group (ATORG) convened a multi-disciplinary panel of 27 experts to develop a consensus statement on the clinical application of ctDNA-based MRD testing in early-stage resected NSCLC, using a structured Delphi methodology. Statements were organized into broad thematic domains: Assay validity and standardization; Harmonization in research and trials; Clinical application; Challenges in implementation; Consensus recommendations; Infrastructure for regional MRD adoption; and Roadmap for pragmatic trials.

RESULTS: A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling timepoints and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. While current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes.

CONCLUSION: These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

PMID:41903701 | DOI:10.1016/j.jtho.2026.103696